Migraine studies consistently have low enrollment of non-White and/or Hispanic participants. This exploratory analysis assesses burden, treatment interventions, and care in people with high-frequency migraine and medication overuse (HFM + MO) in three racial/ethnic groups in the United States that responded to the Migraine Report Card online survey. The Migraine Report Card survey was fielded to adults (≥ 18 years). Eligible respondents reported current or previous HFM + MO (≥ 8 days/month with headache and ≥ 10 days/month of acute headache medication use over the last few months) and screened positive for migraine using the ID Migraine™ screener. Survey questions pertained to living with migraine, healthcare-patient communication, and treatment use and access. Subgroups large enough for analysis included non-Hispanic White, non-Hispanic Black, and Hispanic respondents currently experiencing HFM + MO. Acute medication optimization was assessed with the 4-item Migraine Treatment Optimization Questionnaire. Raw data were weighted to the US adult population. A total of 414 respondents currently experiencing HFM + MO were included in this analysis (White, n = 293; Black, n = 46; Hispanic, n = 75). In this population, despite similarities in migraine and insurance status, 54

Background Migraine is a disabling neurologic disease that can fluctuate over time in severity, frequency, and acute medication use. Harris Poll Migraine Report Card was a US population-based survey to ascertain quantifiable distinctions amongst individuals with current versus previous high-frequency headache/migraine and acute medication overuse (HFM+AMO). The objective of this report is to compare self-reported experiences in the migraine journey of adults with HFM+AMO to those who previously experienced HFM+AMO but currently have a sustained reduction in headache/migraine frequency and acute medication use. Methods An online survey was available to a general population panel of adults (≥18 years) with migraine per the ID Migraine™ screener. Respondents were classified into “current HFM+AMO” (within the last few months had ≥8 headache days/month and ≥10 days/month of acute medication use; n =440) or “previous HFM+AMO” (previously had HFM+AMO, but within the last few months had ≤7 headache days/month and ≤9 days/month of acute medication use; n =110). Survey questions pertained to demographics, diagnosis, living with migraine, healthcare provider (HCP) communication, and treatment. Results Participants in the current HFM+AMO group had 15.2 monthly headache days and 17.4 days of monthly acute medication use in last few months compared to 4.2 and 4.1 days for the previous HFM+AMO group, respectively. Overall, current preventive pharmacologic treatment use was low (15-16%; P >0.1 for current vs previous) in both groups. Previous HFM+AMO respondents reported better current acute treatment optimization. More respondents with current (80%) than previous HFM+AMO (66%) expressed concern with their current health ( P <0.05). More than one-third of both groups wished their HCP better understood their mental/emotional health (current 37%, previous 35%; P >0.1 for current vs previous) and 47% (current) to 54% (previous) of respondents worried about asking their HCP too many questions ( P >0.1 for current vs previous). Conclusion Apart from optimization of acute medication, medical interventions did not significantly differentiate between the current and previous HFM+AMO groups. Use of preventive pharmacological medication was low in both groups. Adults with current HFM+AMO more often had health concerns, yet both groups expressed concerns of disease burden. Optimization of acute and preventive medication and addressing mental/emotional health concerns of patients are areas where migraine care may impact outcomes regardless of their disease burden. Graphical Abstract

Abstract Background High-frequency headache/migraine (HFM) and overuse of acute medication (medication overuse [MO]) are associated with increased disability and impact. Experiencing both HFM and MO can potentially compound impacts, including stigma; however, evidence of this is limited. The objective of this report was to evaluate self-reported stigma, health-related quality of life (HRQoL), disability, and migraine symptomology in US adults with HFM + MO from the Harris Poll Migraine Report Card survey. Methods US adults (≥ 18 yrs., no upper age limit) who screened positive for migraine per the ID Migraine™ screener completed an online survey. Participants were classified into “current HFM + MO” (≥ 8 days/month with headache/migraine and ≥ 10 days/month of acute medication use over last few months) or “previous HFM + MO” (previously experienced HFM + MO, headaches now occur ≤ 7 days/month with ≤ 9 days/month of acute medication use). Stigma, HRQoL, disability, and most bothersome symptom (MBS) were captured. The validated 8-item Stigma Scale for Chronic Illnesses (SSCI-8) assessed internal and external stigma (scores ≥ 60 are clinically significant). Raw data were weighted to the US adult population. Statistically significant differences were determined by a standard t-test of column proportions and means at the 90% (p < 0.1) and 95% (p < 0.05) confidence levels. Results Participants (N = 550) were categorized as having current (n = 440; mean age 41.1 years; 54% female; 57% White, not Hispanic; 24% Hispanic; 11% Black, not Hispanic) or previous (n = 110; mean age 47.2 years; 49% female; 75% White, not Hispanic; 13% Hispanic; 4% Black, not Hispanic) HFM + MO. Compared to those with previous HFM + MO (21%), adults with current HFM + MO were more likely to experience clinically significant levels of stigma (47%). Men with current HFM + MO (52% compared to men with previous HFM + MO [25%] and women with current [41%] or previous [18%] HFM + MO), non-Hispanic Black (51% compared to White, not Hispanic [45%] and Hispanic [48%] current HFM + MO groups and White, not Hispanic previous HFM + MO [12%]), current HFM + MO aged 18–49 years (50% compared to those with current HFM + MO aged ≥ 50 years [33%] and those with previous HFM + MO aged 18–49 [34%] and ≥ 50 years [4%]), and employed respondents (53% current and 29% previous compared to those not employed [32% current and 12% previous]) reported higher rates of clinically significant stigma. Those with current HFM + MO were more likely to have worse HRQoL and disability due to headache/migraine. Respondents aged ≥ 50 years with current HFM + MO were more likely than respondents aged 18–49 years with current HFM + MO to indicate that their overall quality of life (66% vs. 52%) and their ability to participate in hobbies/activities they enjoy were negatively impacted by headache/migraine (61% vs. 49%). Pain-related symptoms were identified as the MBS. Conclusions Together these data suggest that current and previous HFM + MO can be associated with undesirable outcomes, including stigma and reduced HRQoL, which were greatest among people with current HFM + MO, but still considerable for people with previous HFM + MO. Graphical abstract

Longer periods between headache episodes (interictal periods) may provide greater time for the nervous system to reset from a previous episode, potentially improving disease status and health-related quality of life. This post hoc analysis evaluated this hypothesis by associating patients’ longest interictal periods with improvements in patient-reported outcomes. PROMISE-2 (NCT02974153) was a double-blind, placebo-controlled study evaluating eptinezumab for preventive treatment of chronic migraine (N = 1072). Daily electronic diary data from Weeks 1–12 and Weeks 1–24 were used to identify interictal periods, defined as days between headache episodes. For each patient, the longest interictal period within these intervals was identified and categorized (1–4, 5–9, 10–14, > 14, and > 21 days). For each category, the following patient-reported outcomes were assessed: 6-item Headache Impact Test (HIT-6), Patient Global Impression of Change (PGIC), and patient-identified most bothersome symptom (PI-MBS). Excluding interictal periods with > 10

What is this summary about? The Harris Poll Migraine Report Card was a survey about people's experiences and challenges with headaches and migraine. The survey was conducted from December 9, 2021, to January 10, 2022, in the United States. The people who took the survey had frequent headaches/migraine attacks (on 8 or more days per month) and used acute headache/migraine medication to relieve head pain and other symptoms (on 10 or more days per month). This summary focuses on the responses of adults with frequent headaches and frequent acute medication use at the time of the survey or within the few months (not specified) before the survey (and not those who previously had frequent headaches and frequent acute medication use at some point in their life prior to the survey). The group of people who took the survey will be called 'respondents'. The term 'headaches' can mean any type of headache including as part of a migraine attack, a tension type headache, or another unknown headache type. All respondents screened positive for having migraine, so many of the headaches they reported on may have been a migraine headache or part of a migraine attack. What were the results? Over 50% of respondents said their headaches affected their overall quality of life. Many respondents wished their healthcare provider who was managing their headaches understood more about how headaches affect their mental well-being, how much pain their headaches cause, and why they get headaches. 80% of respondents had concerns about their overall health. Over 60% of respondents said they have experienced anxiety and/or depression. In this survey, although all respondents were eligible to receive a preventive headache/migraine medication because of their headache frequency, only 15% were taking one. What do the results of the survey mean? The findings from this survey showed many ways that headaches/migraine care can improve, including talking about mental and emotional well-being, making sure the treatment plan works and does not have side effects that cannot be tolerated, and trying to prevent headaches/migraine from occurring.

ObjectiveThis post hoc analysis of the PREVAIL study explored the effectiveness of eptinezumab for up to 2 years of open-label treatment in the subgroup of patients with chronic migraine who had a confirmed diagnosis of medication-overuse headache (MOH) at screening.BackgroundMOH is a disabling and costly secondary headache disorder characterized by increased headache frequency and/or severity with increased acute headache medication use. Eptinezumab, an anti-calcitonin gene-related peptide monoclonal antibody, reduces headache frequency, severity, and associated disability and improves functioning and health-related quality of life as a preventive migraine therapy; short-term benefits in patients with concurrent MOH have also been reported.MethodsParticipants received up to eight quarterly intravenous infusions of eptinezumab 300 mg in the phase 3, single-arm, open-label PREVAIL study. Safety and patient-reported outcome measures (Migraine Disability Assessment [MIDAS], 6-item Headache Impact Test [HIT-6], patient-identified most bothersome symptom [PI-MBS], Patient Global Impression of Change [PGIC], and 36-item Short-Form Health Survey [SF-36]) were conducted at predefined intervals. Patients were observed up to 20 weeks after their last infusion (Week 104).ResultsA total of 49/128 (38.3%) patients enrolled in PREVAIL had an MOH diagnosis at screening. In the MOH subgroup, long-term eptinezumab treatment was associated with reductions in headache frequency (43/49 [87.8%] patients reported >= 50% reduction in MIDAS-derived headache days at >= 1 visit), severity (2.2-point reduction [on a 10-point scale]), disability (mean MIDAS total score reduction of 51.9 points), and impact (mean HIT-6 total score reduction of 9.7 points) at Week 104. Most patients described a "much improved" or "very much improved" status by Week 48 (PI-MBS, 31/46 [67.4%]) and Week 104 (PGIC, 31/36 [86.1%]). Health-related quality of life improvements in the SF-36 were also observed.ConclusionEptinezumab preventive therapy in patients with chronic migraine showed benefits that extended to the subset of patients with concomitant MOH. In this open-label study, we looked at the effects of eptinezumab in a subset of patients with chronic migraine and medication-overuse headache (MOH). Our results showed that after 2 years of treatment with eptinezumab, these patients reported that their headache days had decreased by more than half, their headaches were less severe, and that headaches interfered much less with their lives. Eptinezumab preventive therapy in patients with chronic migraine showed benefits for the group of patients with MOH.

Background In individuals with migraine, attacks may increase in frequency, severity, or both. Preventing migraine progression has emerged as a treatment goal in headache subspecialty practice, but there may be less awareness in general neurology or primary care settings where most people with migraine who seek treatment consult. Herein, we review the definition of and risk factors for migraine progression and consider strategies that could reduce its risk. Methods A group of headache expert healthcare professionals, clinicians, and researchers reviewed published evidence documenting factors associated with increased or decreased rates of migraine progression and established expert opinions for disease management recommendations. Strength of evidence was rated as good, moderate, or based solely on expert opinion, using modified criteria for causation developed by AB Hill. Results Migraine progression is commonly operationally defined as the transition from ≤ 15 to ≥ 15 monthly headache days among people with migraine; however, this does not necessarily constitute a fundamental change in migraine biology and other definitions should be considered. Established and theoretical key risk factors for migraine progression were categorized into five domains: migraine disease characteristics, treatment-related factors, comorbidities, lifestyle/exogenous factors, and demographic factors. Within these domains, good evidence supports the following risk factors: poorly optimized acute headache treatment, cutaneous allodynia, acute medication overuse, selected psychiatric symptoms, extra-cephalic chronic pain conditions, metabolism-related comorbidities, sleep disturbances, respiratory conditions, former/current high caffeine intake, physical inactivity, financial constraints, tobacco use, and personal triggers as risk factors. Protective actions that may mitigate migraine progression are sparsely investigated in published literature; our discussion of these factors is primarily based on expert opinion. Conclusions Recognizing risk factors for migraine progression will allow healthcare providers to suggest protective actions against migraine progression (Supplementary Fig. 1). Intervention studies are needed to weight the risk factors and test the clinical benefit of hypothesized mitigation strategies that emerge from epidemiological evidence.

Dans les études PROMISE-1 et PROMISE-2, une réponse à la 1ère administration d'eptinezumab (réduction ≥ 50 % du nombre de jours mensuels de migraine [JMM]) a été observée chez ∼50–60 % des patients. Évaluer les facteurs prédictifs d'une réponse à la 2nd administration d'eptinezumab (évaluation sur la période semaines 13–24), chez des patients migraineux rapportant une réponse initiale sous-optimale sur la période semaines 1–12. Cette analyse post hoc des études de phase 3 dans la migraine épisodique (PROMISE-1) et chronique (PROMISE-2) a inclus les patients qui présentaient une réponse sous-optimale après la 1ère administration (définie par une réduction du nombre JMM < 50 % sur les semaines 1–12) et dont les données PRO – Patient Reported Outcomes – étaient disponibles aux semaines 12 et 24. Les groupes eptinezumab 100 mg et 300 mg ont été poolés. L'analyse a inclus 416/888 patients (46,8 %) de PROMISE-1 et 479/1072 patients (44,7 %) de PROMISE-2 présentant une réponse initiale sous-optimale. Parmi eux, la proportion qui étaient répondeurs à la 2nd administration était de 37,0 % (71/192) avec eptinezumab et 33,9 % (42/124) avec le placebo (PROMISE-1), et 28,8 % (79/274) avec eptinezumab et 18,5 % (38/205) avec le placebo (PROMISE-2). Les facteurs prédictifs d'une réponse à la 2nd administration incluaient la variation du nombre de JMM (en %) et la variation du score HIT-6. N/A. Une 2nd administration d'eptinezumab peut bénéficier aux patients souffrant de migraine qui ne présentent pas une réduction ≥ 50 % du nombre de JMM après la 1ère administration d'eptinezumab.

Objective: To evaluate self-reported stigma in US adults with high-frequency headache/migraine (HFM) and acute medication overuse (AMO). Background: While the increasing frequency of migraine is associated with greater disability and comorbidities, data of stigma relating to HFM+AMO are limited. Design/Methods: US adults (≥18yr) who screened positive for migraine on the validated "ID Migraine" completed a 15-minute online survey. Respondents were classified into "current HFM+AMO" (≥8 days/month with headache/migraine with ≥10 days/month of acute headache medication use) or "previous HFM+AMO" (previously experienced HFM, but currently experiencing headache ≤7 days/month with ≤9 days/month of acute medication use). The 8-item Stigma Scale for Chronic Illnesses (SSCI-8) assessed internal and external stigma. Statistically significant differences were detected by standard t-test at 90% and 95% confidence levels. Results: US adults (N=550) were classified as having current (n=440, 54% women, mean age 41.1yr, 57% White) or previous (n=110, 49% women, mean age 47.2yr, 75% White) HFM+AMO. Adults with current HFM+AMO were more likely than those with previous HFM+AMO to always/often experience 6 of 8 SSCI-8 measures (P<0.1). Women with current HFM+AMO were more likely than women with previous HFM+AMO to always/often experience 7 SSCI-8 measures (P<0.1). Of those with current HFM+AMO, men were more likely than women to always/often feel embarrassed about their illness, feel people avoided looking at them, and say people were unkind to them (P<0.1); younger respondents (18–49yr) were more likely than older respondents (≥50yr) to always/often experience 6 SSCI-8 measures (P<0.1); and Black respondents were more likely than white respondents to always/often feel embarrassed and feel that people were unkind to them (P<0.1). Conclusions: US adults with current HFM+AMO were more likely to experience stigma due to migraine than those with previous HFM+AMO, particularly women. Certain stigma experiences were significantly more common in men, younger adults, and Black adults with current HFM+AMO. Disclosure: Dr. Buse has received personal compensation for serving as an employee of Vector Psychometric Group. Dr. Buse has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Abbvie-Allergan. Dr. Buse has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Amgen. Dr. Buse has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Lilly. Dr. Buse has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Lundbeck. Dr. Buse has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Collegium. Dr. Buse has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Lilly. Dr. Buse has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Abbvie-Allergan. Dr. Buse has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Lundbeck. Dr. Buse has received personal compensation in the range of $0-$499 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Current Pain and Headache Reports. The institution of Dr. Buse has received research support from Amgen. Dr. Cady has received personal compensation for serving as an employee of Lundbeck. Dr. Cady has stock in Alder Biopharmaceutical. Dr. Starling has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Amgen. Dr. Starling has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Axsome Therapeutics. Dr. Starling has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Lundbeck. Dr. Starling has received personal compensation in the range of $0-$499 for serving as a Consultant for Med-IQ. Dr. Starling has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Medscape. Dr. Starling has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Satsuma. Dr. Starling has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Neurolief. Dr. Starling has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Abbvie. Dr. Starling has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Everyday Health. Dr. Starling has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Allergan. Dr. Starling has received personal compensation in the range of $500-$4,999 for serving as a Consultant for WebMD. Mrs. Buzby has received personal compensation for serving as an employee of Coalition for Headache and Migraine Patients. Mrs. Buzby has a non-compensated relationship as a Advisor with Lundbeck that is relevant to AAN interests or activities. Mr. Spinale has received personal compensation for serving as an employee of The Harris Poll. Ms. Steinberg has received personal compensation for serving as an employee of The Harris Poll. Steven Kymes has received personal compensation for serving as an employee of Lundbeck. Steven Kymes has received personal compensation in the range of $0-$499 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for American Journal of Ophthalmology. Steven Kymes has received research support from Emmes Corporation.

Treatment target goals for patients receiving preventive migraine treatment are complicated to assess and not achieved by most patients. A headache “number” could establish an understandable treatment target goal for patients with chronic migraine (CM). This study investigates the clinical impact of reduced headache frequency to ≤ 4 monthly headache days (MHDs) as a treatment-related migraine prevention target goal. All treatment arms were pooled for analysis from the PROMISE-2 trial evaluating eptinezumab for the preventive treatment of CM. Patients (N = 1072) received eptinezumab 100 mg, 300 mg, or placebo. Data for the 6-item Headache Impact Test (HIT-6), Patient Global Impression of Change (PGIC), and acute medication use days were combined for all post-baseline assessments and analyzed by MHD frequency (≤ 4, 5–9, 10–15, > 15) in the 4 weeks preceding assessment. Based on pooled data, the percentage of patient-months with ≤ 4 MHDs associated with “very much improved” PGIC was 40.9 https://clinicaltrials.gov/ct2/show/NCT02974153 ).

WHAT IS THIS SUMMARY ABOUT?:This is a summary of three articles describing preventive treatment of migraine in participants with a diagnosis of both chronic migraine and medication-overuse headache in a study called PROMISE-2 (PRevention Of Migraine via Intravenous ALD403 Safety and Efficacy-2). People living with chronic migraine and medication-overuse headache have one of the most disabling, costly, and difficult-to-treat headache disorders. WHAT WERE THE RESULTS?:After preventive migraine treatment with eptinezumab (trade name Vyepti), participants with chronic migraine and medication-overuse headache experienced fewer migraine days, a reduced severity of migraine attacks, and a reduced use of acute medication. More participants receiving eptinezumab treatment no longer met the definition of either chronic migraine or medication-overuse headache throughout the study when compared with those receiving placebo. WHAT DO THE RESULTS MEAN?:Eptinezumab is beneficial for people who often use acute medication(s) due to frequent headache episodes or migraine attacks.

Objective: To analyze the migraine-preventive efficacy of eptinezumab in patients with a dual diagnosis of chronic migraine (CM) and medication-overuse headache (MOH). Background: Eptinezumab, a humanized anti-calcitonin gene-related peptide monoclonal antibody, is approved for the preventive treatment of migraine and has demonstrated effectiveness in patients with CM. Design/Methods: PROMISE-2 (NCT02974153), a double-blind, placebo-controlled, phase 3 study, randomized adults with CM to intravenous eptinezumab 100mg, 300mg, or placebo at day 0 and week 12 (wk12), for 24 weeks total treatment. Endpoints included changes in monthly migraine days (MMDs), monthly days of acute headache medication (AHM) use, percentage of patients below International Classification of Headache Disorders (ICHD) thresholds for CM and MOH, and assessments of patient-reported outcomes (PROs): 6-item Headache Impact Test (HIT-6), Patient Global Impression of Change (PGIC), and patient-identified most bothersome symptom (PI-MBS). Results: At baseline, 431/1072 (40.2%) patients with CM (eptinezumab 100mg [n=139]; 300mg [n=147]; placebo [n=145]) were diagnosed with MOH and averaged 16.7 MMDs. At wk12, mean MMDs decreased 8.4 (100mg) and 8.6 (300mg) from baseline, versus 5.4 placebo (P<0.0001 for both doses). At 24wks, 29.0% of eptinezumab-treated patients were below CM and MOH diagnostic thresholds versus 6.3% with placebo. Total monthly AHM use decreased 9.8 days [BR1] (100mg) and 8.4 days [BR2] (300mg) during wks 1–12 vs 5 days [BR3] with placebo. HIT-6 total scores improved 7.0 (100mg) and 7.8 (300mg) vs 4.1 points (placebo) at wk12. At wk12, 58.5% (100mg) and 67.4% (300mg) of patients indicated PGIC was "much" or "very much" improved vs 35.8% placebo. PI-MBS improvement with eptinezumab treatment over placebo was similar to PGIC. Conclusions: This post hoc analysis of patients with dual diagnoses of CM and MOH suggests that eptinezumab treatment resulted in greater reductions in MMDs and AHM use compared with placebo and is associated with sustained, clinically meaningful improvements in PROs. Disclosure: Dr. Marmura has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Lundbeck. Dr. Marmura has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Supernus. Dr. Marmura has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Axsome. Dr. Marmura has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Satsuma. Dr. Marmura has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Upsher-Smith. Dr. Marmura has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Lundbeck. Dr. Marmura has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Theranica. Dr. Marmura has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Amgen/Novartis. Dr. Marmura has received personal compensation in the range of $50,000-$99,999 for serving on a Speakers Bureau for Lilly. Dr. Marmura has stock in Curelator. The institution of Dr. Marmura has received research support from Teva. The institution of Dr. Marmura has received research support from AbbVie. Dr. Marmura has received publishing royalties from a publication relating to health care. Dr. Marmura has received publishing royalties from a publication relating to health care. Dr. Marmura has received publishing royalties from a publication relating to health care. Dr. Diener has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Lundbeck. Dr. Diener has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for TEVA. Dr. Diener has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Lundbeck. Dr. Diener has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Springer. Dr. Diener has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Thieme. The institution of Dr. Diener has received research support from German Research Council. Dr. Cowan has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Lundbeck. Dr. Cowan has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Teva. Dr. Cowan has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Abbvie. Dr. Cowan has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Lilly. Dr. Cowan has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biohaven. Dr. Cowan has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for lundbeck. Dr. Cowan has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for biohavenn. Dr. Cowan has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Abbviie. Dr. Cowan has stock in Percept. Dr. Cowan has received intellectual property interests from a discovery or technology relating to health care. Dr. Cowan has received intellectual property interests from a discovery or technology relating to health care. Dr. Cowan has received publishing royalties from a publication relating to health care. Dr. Starling has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Amgen. Dr. Starling has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Axsome Therapeutics. Dr. Starling has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Lundbeck. Dr. Starling has received personal compensation in the range of $0-$499 for serving as a Consultant for Med-IQ. Dr. Starling has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Medscape. Dr. Starling has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Satsuma. Dr. Starling has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Neurolief. Dr. Starling has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Abbvie. Dr. Starling has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Everyday Health. Dr. Starling has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Allergan. Dr. Starling has received personal compensation in the range of $500-$4,999 for serving as a Consultant for WebMD. Joe Hirman, PhD has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Lundbeck . Joe Hirman, PhD has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Impel NeuroPharma. Thomas Brevig has received personal compensation for serving as an employee of H. Lundbeck A/S. Thomas Brevig has received personal compensation for serving as an employee of Gedeon Richter Plc.. Thomas Brevig has stock in H. Lundbeck A/S. Dr. Cady has received personal compensation for serving as an employee of Lundbeck. Dr. Cady has stock in Alder Biopharmaceutical.

Objective: To demonstrate the lack of a "wearing off effect" with eptinezumab in preventive migraine treatment. Background: A "wearing off effect" is described as a positive response to treatment with a shorter duration of benefit than expected. Design/Methods: PROMISE-1 (NCT02559895) and PROMISE-2 (NCT02974153) were both phase 3, randomized, double-blind, placebo-controlled studies that evaluated the efficacy and safety of eptinezumab (administered every 12 weeks) for migraine prevention in adults with episodic or chronic migraine, respectively. PROMISE-1 and PROMISE-2 captured monthly migraine days (MMDs) for up to 48 weeks and 24 weeks of treatment, respectively. Using data on the change in MMDs, a post hoc closed testing analysis investigated the consistency of effect during the first dosing interval. The percentage of patients experiencing a migraine attack at intervals reduced by a single day was analyzed beginning with the primary endpoint interval (Weeks 1–12, or Days 1–84). Results: In both studies, eptinezumab 100mg and 300mg demonstrated greater reductions vs placebo in MMDs over 4-week intervals that were sustained across the respective treatment periods. The closed testing analysis showed that both doses achieved nominally significant differences (P<0.05) from Day 84 to Day 1 independently, indicating that eptinezumab was effective beginning Day 1 after dosing. Reductions from baseline were greater than the reduction for placebo across the entire curve. Similar magnitudes of effect over each 4-week interval at the population level suggests the onset of the migraine preventive effect of eptinezumab can be observed on Day 1 following initial dosing, with the effect sustained through the full 12 weeks. Conclusions: No statistically significant differences were found between the percentages of patients reporting migraine attack reduction on Day 1 and on any day through Day 84. In both pivotal trials for eptinezumab, there is no significant "wearing off" of eptinezumab's preventive benefit observed through Day 84. Disclosure: Dr. Cady has received personal compensation for serving as an employee of Lundbeck. Dr. Cady has stock in Alder Biopharmaceutical. Meghana Karnik-Henry has received personal compensation for serving as an employee of Lundbeck. Divya Asher has received personal compensation for serving as an employee of Lundbeck. Divya Asher has received personal compensation for serving as an employee of AbbVie. Seema Soni-Brahmbhatt has nothing to disclose. Dr. Dodick has received personal compensation for serving as an employee of Mayo Clinic. Dr. Dodick has received personal compensation for serving as an employee of Atria Health. Dr. Dodick has received personal compensation for serving as an employee of Thomas Jefferson University . Dr. Dodick has received personal compensation for serving as an employee of Norwegian University of Science and Technology. Dr. Dodick has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Amgen. Dr. Dodick has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Allergan. Dr. Dodick has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Abbvie. Dr. Dodick has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biohaven. Dr. Dodick has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biopharm Communications. Dr. Dodick has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Lundbeck. Dr. Dodick has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Eli Lilly. Dr. Dodick has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Teva. Dr. Dodick has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Inside Practice Australia. Dr. Dodick has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Clinical Education Alliance. Dr. Dodick has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Genentech. Dr. Dodick has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Headache Cooperative of the Pacific . Dr. Dodick has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Medica Communications. Dr. Dodick has received personal compensation in the range of $500-$4,999 for serving as a Consultant for MJ Healthcare. Dr. Dodick has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Nocira. Dr. Dodick has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Praxis. Dr. Dodick has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Revance . Dr. Dodick has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Synapse Medical Communications. Dr. Dodick has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Vector Psychometrics. Dr. Dodick has received personal compensation in the range of $0-$499 for serving as a Consultant for Ayya Biosciences. Dr. Dodick has received personal compensation in the range of $0-$499 for serving as a Consultant for Theranica. Dr. Dodick has received personal compensation in the range of $100,000-$499,999 for serving as a Consultant for Atria. Dr. Dodick has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for WebMD. Dr. Dodick has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Thomas Jefferson University. Dr. Dodick has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Medforce. Dr. Dodick has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Precision HEOR. Dr. Dodick has received personal compensation in the range of $0-$499 for serving as an officer or member of the Board of Directors for KingDevick Technologies. Dr. Dodick has received personal compensation in the range of $1,000,000+ for serving as an officer or member of the Board of Directors for Precon Health. Dr. Dodick has received personal compensation in the range of $0-$499 for serving as an officer or member of the Board of Directors for Ontologics. Dr. Dodick has received personal compensation in the range of $0-$499 for serving as an officer or member of the Board of Directors for Matterhorn. Dr. Dodick has received personal compensation in the range of $0-$499 for serving as an officer or member of the Board of Directors for Axon Therapeutics. Dr. Dodick has received personal compensation in the range of $0-$499 for serving as an officer or member of the Board of Directors for Cephalgia Group. Dr. Dodick has stock in Healint. Dr. Dodick has stock in Theranica. Dr. Dodick has stock in Aural Analytics . Dr. Dodick has stock in Epien. Dr. Dodick has stock in Matterhorn. Dr. Dodick has stock in Ontologics. Dr. Dodick has stock in Precon Health. Dr. Dodick has stock in King Devick Technologies. Dr. Dodick has stock in Nocira. Dr. Dodick has stock in Exsano. Dr. Dodick has stock in Palion. Dr. Dodick has stock in AYYA Biosciences. Dr. Dodick has stock in Perfood. Dr. Dodick has stock in Cephalgia Group. Dr. Dodick has stock in Atria Health. Dr. Dodick has stock in Man and Science. The institution of Dr. Dodick has received research support from Department of Defense. The institution of Dr. Dodick has received research support from Patient Centered Outcomes Research Institute. The institution of Dr. Dodick has received research support from Henry Jackson Foundation. Dr. Dodick has received intellectual property interests from a discovery or technology relating to health care. Dr. Dodick has received intellectual property interests from a discovery or technology relating to health care. Dr. Dodick has received intellectual property interests from a discovery or technology relating to health care. Dr. Dodick has received publishing royalties from a publication relating to health care. Dr. Dodick has received publishing royalties from a publication relating to health care. Dr. Dodick has received publishing royalties from a publication relating to health care. Dr. Dodick has a non-compensated relationship as a Chair with American Brain Foundation that is relevant to AAN interests or activities. Dr. Dodick has a non-compensated relationship as a Committee member/Course Director with American Academy of Neurology that is relevant to AAN interests or activities. Dr. Dodick has a non-compensated relationship as a Chair/Immediate Past Chair with American Migraine Foundation that is relevant to AAN interests or activities. Dr. Dodick has a non-compensated relationship as a Chair Global Patient Advocacy Coalition with International Headache Society that is relevant to AAN interests or activities.

Background Real-world evidence (RWE)—based on information obtained from sources such as electronic health records (EHRs), claims and billing databases, product and disease registries, and personal devices and health applications—is increasingly used to support healthcare decision making. There is variability in the collection of EHR data, which includes “structured data” in predefined fields (e.g., problem list, open claims, medication list, etc.) and “unstructured data” as free text or narrative. Healthcare providers are likely to provide more complete information as free text, but extracting meaning from these fields requires newer technologies and a rigorous methodology to generate higher-quality evidence. Herein, an approach to identify concepts associated with the presence and progression of migraine was developed and validated using the complete patient record in EHR data, including both the structured and unstructured portions. Methods “Traditional RWE” approaches (i.e., capture from structured EHR fields and extraction using structured queries) and “Advanced RWE” approaches (i.e., capture from unstructured EHR data and processing by artificial intelligence [AI] technology, including natural language processing and AI-based inference) were evaluated against a manual chart abstraction reference standard for data collected from a tertiary care setting. The primary endpoint was recall; differences were compared using chi square. Results Compared with manual chart abstraction, recall for migraine and headache were 66.6% and 29.6%, respectively, for Traditional RWE, and 96.8% and 92.9% for Advanced RWE; differences were statistically significant (absolute differences, 30.2% and 63.3%; P < 0.001). Recall of 6 migraine-associated symptoms favored Advanced RWE over Traditional RWE to a greater extent (absolute differences, 71.5–88.8%; P < 0.001). The difference between traditional and advanced techniques for recall of migraine medications was less pronounced, approximately 80% for Traditional RWE and ≥ 98% for Advanced RWE ( P < 0.001). Conclusion Unstructured EHR data, processed using AI technologies, provides a more credible approach to enable RWE in migraine than using structured EHR and claims data alone. An algorithm was developed that could be used to further study and validate the use of RWE to support diagnosis and management of patients with migraine.

Objective: To assess the relative importance of 5 attributes in the choice of preventive migraine treatment from the patient perspective. Background: Anti-CGRP monoclonal antibodies and onabotulinumtoxinA have demonstrated efficacy and tolerability, the two most important migraine treatment attributes. Design/Methods: This non-interventional, cross-sectional study enrolled US adults with self-reported migraine diagnoses, who experienced ≥5 monthly migraine days, and had tried ≥2 prescription migraine treatments. A 25-minute discrete choice online survey was used to assess treatment preferences by having respondents select between two profiles that varied in attributes: speed of onset (24hr, 1wk, or 3mo), durability of prevention (wears off 1wk prior to next dose, 2wks prior to next dose, or does not wear off), mode of administration (IV, self-injection, or cranial injections), administration setting (at-home or in-office), and dosing frequency (1mo or 3mo). Hierarchical Bayes modeling estimated attribute-level preference weights. A latent class analysis identified subgroups that differed in their preferences. Results: 604 patients were analyzed. Mode of administration, durability of prevention, and speed of onset had the highest relative importance; administration setting and frequency of dosing had the lowest. Four groups with differing preferences were identified: those preferring auto-injection (n=128, 21%); those averse to cranial injections (n=189, 31%); those preferring faster speed of onset (n=158, 26%); and those preferring longer durability and clinicians to administer treatment (n=129, 21%). Except for those preferring auto-injection, all groups were willing to accept IV administration to achieve other treatment goals, indicating that three-fourths of participants were not averse to IV infusion as a route of administration. Conclusions: Among people living with migraine who have ≥5 monthly migraine days, important attributes of preventive migraine treatment were mode of administration, durability of effect, and speed of onset. Infusion as a route of administration was not considered a barrier for most patients. Disclosure: Dr. Schwedt has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Allergan. Dr. Schwedt has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biohaven. Dr. Schwedt has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Eli Lilly. Dr. Schwedt has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Lundbeck. Dr. Schwedt has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis. Dr. Schwedt has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Ipsen. Dr. Schwedt has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Tonix Pharma. Dr. Schwedt has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Satsuma. Dr. Schwedt has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Biodelivery Science. Dr. Schwedt has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Abbvie. Dr. Schwedt has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Axsome. Dr. Schwedt has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Collegium. Dr. Schwedt has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Linpharma. Dr. Schwedt has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Theranica. Dr. Schwedt has stock in Aural Analytics. Dr. Schwedt has stock in Nocira. The institution of Dr. Schwedt has received research support from Amgen. The institution of Dr. Schwedt has received research support from National Institutes of Health. The institution of Dr. Schwedt has received research support from United States Department of Defense. The institution of Dr. Schwedt has received research support from Patient Centered Outcomes Research Institute. The institution of Dr. Schwedt has received research support from SPARK Neuro. The institution of Dr. Schwedt has received research support from Henry Jackson Foundation. Dr. Schwedt has received intellectual property interests from a discovery or technology relating to health care. Dr. Schwedt has received publishing royalties from a publication relating to health care. Dr. Martin has received personal compensation for serving as an employee of Cerner Enviza. The institution of Dr. Martin has received research support from Lundbeck LLC. Steven Kymes has received personal compensation for serving as an employee of Lundbeck. Steven Kymes has received personal compensation in the range of $0-$499 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for American Journal of Ophthalmology. Steven Kymes has received research support from Emmes Corporation. Dr. Talon has nothing to disclose. Ms. Lee has received personal compensation for serving as an employee of Lundbeck A/S. Dr. Cady has received personal compensation for serving as an employee of Lundbeck. Dr. Cady has stock in Alder Biopharmaceutical. Divya Asher has received personal compensation for serving as an employee of Lundbeck. Divya Asher has received personal compensation for serving as an employee of AbbVie. Meghana Karnik-Henry has received personal compensation for serving as an employee of Lundbeck. Ms. Mulvihill has received personal compensation for serving as an employee of Cerner Enviza, an Oracle Company. Ms. Bates has nothing to disclose. Ms. Beusterien has received personal compensation for serving as an employee of Cerner Enviza.

Objective: To define and validate the accuracy of a scalable framework model using electronic health record (EHR) data to measure migraine treatment and prevention outcomes by using artificial intelligence (AI). Background: In disease areas such as migraine that report subjective measures (ie. severity, descriptors, etc.) as outcomes, extraction and validation of real-world evidence (RWE) from EHRs can be challenging. Information required to assess migraine endpoints used in clinical trials are not consistently captured in routine care, limiting the utility of these previously defined endpoints in RWE studies. Design/Methods: Headache specialists defined clinical features found in routinely collected data. EHR data were reviewed by two clinical annotators to create a manual reference standard for features included in the migraine outcome model. Data elements were weighted to define a 10-point scale incorporating headache severity (1–7 points) and associated features (0–3 points). Automation (i.e., AI) extracted features from patient encounters and compared to the reference standard. A 70% agreement threshold (within 1 point) between the human annotator and the automated score was considered sufficient extraction accuracy. AI accuracy in identifying features used to construct the outcome model success was defined as reaching an F1 score of 80% for identifying encounters. Results: From a total of 2,006 encounters, 11 features were included in the model; average automated extraction F1 scores were 92.0% when applied to unstructured data. Automated extraction model scores matched for 77.2% of encounters exactly and were a within 1 point close match for 82.2%, compared with manual extraction scores—well above the 70% match threshold. Conclusions: These data indicate feasibility of AI generated models to generate migraine outcome scores using features commonly captured in real-world settings with high accuracy, providing a scalable approach to EHR-based clinical studies to support migraine prevention and treatment. Disclosure: Steven Kymes has received personal compensation for serving as an employee of Lundbeck. Steven Kymes has received personal compensation in the range of $0-$499 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for American Journal of Ophthalmology. Steven Kymes has received research support from Emmes Corporation. Dr. Cady has received personal compensation for serving as an employee of Lundbeck. Dr. Cady has stock in Alder Biopharmaceutical. Dr. Hindiyeh has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Eli Lilly. Dr. Hindiyeh has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Eli Lilly. Dr. Hindiyeh has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alder/Lundbeck. Dr. Hindiyeh has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Amgen. Dr. Hindiyeh has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Impel. Dr. Hindiyeh has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Lundbeck . Dr. Alexander has received personal compensation for serving as an employee of Verantos. Dr. Alexander has received personal compensation for serving as an employee of BioMarin. Dr. Alexander has stock in BioMarin. Dr. Riskin has received personal compensation for serving as an employee of Verantos.

ObjectiveTo evaluate the effect of eptinezumab on patient-reported outcomes in patients with chronic migraine (CM) and medication-overuse headache (MOH). BackgroundMOH is a secondary headache disorder commonly occurring in patients with CM and associated with functional and psychological impairments. Medication overuse and monthly headache and migraine days were reduced with eptinezumab compared with placebo as published previously; however, these outcomes do not fully capture the burden of migraine and treatment effect. MethodsPROMISE-2 was a phase 3, randomized, double-blind, placebo-controlled trial in adults with CM. Patients were randomized (1:1:1) to receive eptinezumab 100 mg, eptinezumab 300 mg, or placebo (up to 2 doses, 12 weeks apart). Patients completed the following patient-reported outcomes: 6-item Headache Impact Test (HIT-6), Patient Global Impression of Change (PGIC), patient-identified most bothersome symptom (PI-MBS), and 36-item Short-Form Health Survey (SF-36). ResultsA total of 431 CM patients (139, 147, and 145 patients in the eptinezumab 100 mg, eptinezumab 300 mg, and placebo groups, respectively) had MOH diagnosed at screening (40.2% of the total PROMISE-2 population [n = 1072]). In CM with MOH patients, both doses of eptinezumab were associated with clinically meaningful improvements in mean HIT-6 total scores by week 4 and remained improved throughout the 24-week study. Responder rates for individual HIT-6 items were greater with eptinezumab than with placebo at all time points. At week 12, almost twice as many eptinezumab-treated patients indicated the PGIC was "much" or "very much" improved (58.5% [79/135, 100 mg] and 67.4% [95/147, 300 mg] vs. 35.8% [48/134, placebo]). Patients in the eptinezumab groups showed numerically greater improvements over placebo in the PI-MBS and SF-36 scores. ConclusionsThis subgroup analysis in patients with CM/MOH at baseline suggests that eptinezumab treatment is associated with early, sustained, and clinically meaningful improvements in patient-reported outcomes.